Photo Credit: National Cancer Institute/Unsplash

Date: 10 August 2020

Institution: The Ohio State University

Story published in: Journal of Clinical Oncology

Digest: Researchers at OSUCCC – James have identified a biomarker IDH ½ gene in glioma patients. According to their study, glioma patients with mutated IDH ½ gene derive the most significant benefit from PCV-based chemotherapy post-radiation when compared to radiation alone. This kind of study can help clinicians in prescribing personalized treatment options for patients based on their genomic characteristics, and hence they can assure maximum efficiency of the procedure.

Principal investigator Arnab Chakravarti, MD, provide practice-changing data to guide treatment of brain tumor patients diagnosed with gliomas based on their underlying genomic characteristics.

Previous studies of molecular-based prognostic classification for low-grade gliomas led to the WHO’s 2016 reclassification of central nervous system tumor grades, a system that categorizes tumor risk groups based on both anatomical and molecular features. However, follow-up research on the prognostic value of this grading system in clinical outcomes has been limited by the relative rarity of the disease and by having limited access to significant patient populations.

For this new retrospective study, OSUCCC – James researchers sought to determine the prognostic and predictive impact of the WHO-defined molecular subgroups and corresponding molecular alterations of 106 patients who received treatment as part of the NRG Oncology/RTOG 9802 phase III clinical trial. These patients had both comprehensive molecular profiling data based on the WHO-defined molecular groups and information about clinical outcomes available for review.

“Our study is the first prospective, randomized international phase III clinical study to demonstrate that the World Health Organization (WHO) molecular glioma subgroups that are inclusive of the mutant version of the Isocitrate dehydrogenase (IDH 1/2) gene appear to derive greatest benefit from the addition of PCV-based chemotherapy to radiation versus radiation alone,” says Chakravarti, principal investigator of the study and chair of the Department of Radiation Oncology at Ohio State. “PCV-based chemotherapy regimens can be highly effective but can at the same time harbor significant risk for the occurrence of serious toxicities for high-risk, low-grade glioma patients. Hence, it is absolutely critical to identify upfront which of these patients would normally serve to derive greatest survival benefit from a PCV-based chemotherapy regimen while sparing others, who do not derive such survival benefits, from its potentially harmful side-effects.”

Researchers specifically investigated the presence of IDH 1/2 gene mutations by themselves in the tumors and their association with progression-free survival and overall survival among patients. They determined that IDH 1/2 gene mutations were significant predictors of both overall and progression-free survival after adjustment for clinical variables and treatment.

“Treatment with post-radiation chemotherapy was associated with longer overall and progression-free survival among low-grade glioma patients with WHO groups inclusive of IDH gene mutations,” says Chakravarti, who serves as the Klotz Family Chair of Cancer Research and professor and director of the Brain Tumor Program at The Ohio State University College of Medicine. “This new data removes at least some of the controversy about management of low-grade gliomas, primarily related to accurate predictive biomarker classification and treatment selection. We can now definitively use molecular biomarkers to identify people who are likely to reap the greatest benefit from post-radiation chemotherapy and spare those who are unlikely to garner any additional benefit from unnecessary treatment.”

Story Source: The Ohio State University

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